3种药物转运体抑制剂对沙奎那韦在大鼠肠道吸收影响的体外试验  

Study on Effects of 3 Kinds of Drug Transporters Inhibitors on the Intestinal Absorption of Saquinavir in Rats in Vitro

作　　者：刘新民[1] 靳隽[2] 卢乙众[1] 惠红岩[1] 

机构地区：[1]新乡医学院第一附属医院药剂科,河南卫辉453100 [2]新乡医学院医学检验系,河南新乡453000

出　　处：《中国药房》2012年第25期2333-2335,共3页China Pharmacy

摘　　要：目的:体外研究药物转运体P糖蛋白(P-gp)和多药耐药相关蛋白2(Mrp2)特异性抑制剂对沙奎那韦在大鼠肠道吸收的影响。方法:取大鼠用乌拉坦麻醉后,分别取十二指肠、空肠、回肠、结肠各8cm,制备离体肠外翻模型,检测不同肠段在P-gp抑制剂地高辛(10μmol.L-1)和维拉帕米(100μmol.L-1)、Mrp2抑制剂丙磺舒(600μmol.L-1)分别与沙奎那韦(12.5μg.mL-1)的混合Krebs-Ringer缓冲液(K-R液)中孵育5、10、20、30、45、60、90min后对沙奎那韦的累积吸收量;另设含沙奎那韦的K-R液为对照组。结果:沙奎那韦在大鼠十二指肠、空肠、回肠、结肠K-R液中的累积吸收量分别为(7.25±1.23)、(4.96±1.58)、(3.89±0.95)、(5.85±1.21)μg,吸收速率为十二指肠>结肠>空肠>回肠。维拉帕米((10.03±3.56)、(7.52±2.21)、(7.45±1.8)μg)和地高辛((8.76±2.25)、(5.98±1.89)、(6.04±1.92)μg)可显著提高沙奎那韦在结肠、空肠、回肠K-R液中的累积吸收量(P<0.05),对十二指肠无显著影响(P>0.05);丙磺舒对沙奎那韦在各肠段K-R液中的累积吸收量均无显著影响(P>0.05)。结论:P-gp可显著影响沙奎那韦的肠道吸收,Mrp2对沙奎那韦的肠道吸收无影响。OBJECTIVE：To investigate the effects of P-glycoprotein（P-gp） and multidrug resistance-associated protein 2（Mrp2） inhibitors on the intestinal absorption of saquinavir in rats in vitro.METHODS：Rats were anesthetized with urethane and duodenum,jejunum,ileum,and colon were dissected with each intestinal segment of 8 cm.In vitro everted intestinal model was established.Accumulative absorption amount of saquinavir was determined after intestinal segment were cultured in mixtures of P-gp inhibitors digoxin（10 μmol·L-1） and verapamil（100 μmol·L-1） or Mrp2 inhibitor probenecid（600 μmol·L-1） with saquinavir（12.5 μg·mL-1） Krebs-Ringer buffer solution（K-R solution） for 5,10,20,30,45,60,90 min,with K-R solution containing saquinavir as control.RESULTS：When given alone,the cumulative amount of saquinavir in duodenum,jejunum,ileum and colon were（7.25±1.23） μg,（4.96±1.58） μg,（3.89±0.95） μg,（5.85±1.21） μg,and the absorption order of saquinavir in each segment of intestine was as following：duodenum〉colon〉jejunum〉ileum.Combined use of verapamil（（10.03±3.56）、（7.52±2.21）、（7.45±1.8） μg） and digoxin（（8.76±2.25）、（5.98±1.89）、（6.04±1.92） μg） boosted saquinavir absorption in K-R solution of jejunum,ileum and colon（P〈0.05）,but had no significant effect on duodenum（P〉0.05）.In contrast,probenecid had no significant effect on the accumulative absorption amount in K-R solution of each intestinal segment（P〉0.05）.CONCLUSIONS：P-gp plays an important role in absorption of saquinavir in intestine;on the contrary,Mrp2 is not involve in the transport.

关 键 词：沙奎那韦 P糖蛋白 多药耐药相关蛋白2 大鼠 肠道吸收 

分 类 号：R965[医药卫生—药理学]